1. Field of the Invention
The present invention relates to an apparatus for the extracorporeal treatment of disease in which a specific immunological reactant is removed from plasma which has been separated from whole blood and more specifically, to plasma treatment chambers used in the apparatus.
2. Description of the Prior Art
It has been determined that immunological reactants such as antigens, antibodies and antigen-antibody complexes circulating in the blood play an important role in the pathogensis of many diseases. Removal of such pathogenic reactants from blood, and more specifically from the plasma, has been found to be of great therapeutic value.
Systemic lupus erythematosus is one such disease wherein formation of antigen-antibody complexes and deposition of same in tissue causes severe inflammation and removal of such complexes is of therapeutic value.
Also, in resisting and attacking cancerous cells, cytotoxic activity of the body directed to neoplastic cells is blocked by circulating antigens produced by the cancerous cells and interferes with the body's efforts in combatting neoplasia. Here, again, removal of such antigens is of therapeutic value.
Further, the efforts of the body in rejection of tissue transplantation by antibodies circulating in the blood can be alleviated by removal of such antibodies.
Heretofore, various extracorporeal methods and apparatus have been proposed for removing such immunological reactants from plasma.
In practicing such methods for the extracorporeal treatment of disease, whole blood, or plasma only, is circulated through a chamber within which is located a vehicle having thereon an immunoadsorbent agent specific to the immunological reactant to be removed. Typically, the immunoadsorbent agent is an antigen and the immunological reactant is an antibody.
In one apparatus for the extracorporeal treatment of disease, whole blood is removed from a patient into a sterile environment of conduits and chambers. More specifically, the whole blood is withdrawn from the patient by means of a peristaltic pump acting on a tubing which has a needle at one end injected into one arm of the patient. The other end of the tubing is connected to a blood separation chamber in a centrifuge device where the whole blood is centrifuged to segregate and separate the components. Plasma is withdrawn from the separation chamber and passed through a plasma treatment chamber where a specific immunoadsorbent agent on a vehicle, such as a plurality of nylon beads, interacts with a specific immunological reactant in the plasma. Actually, what happens is that the reactant in the plasma attaches itself and becomes bonded to the agent fixed on the vehicle. Substantially reactant free plasma is then withdrawn from the chamber by means of a peristaltic pump, recombined with the other blood components and returned via a tubing and needle to the other arm of the patient.
The extracorporeal treatment of disease has been extensively investigated in connection with the formation of DNA-anti-DNA complexes on a vehicle within a plasma treatment chamber for removing such complexes from the blood. This ability to selectively remove anti-DNA from plasma is a much desired therapeutic measure with respect to systemic lupus erythematosus which is a disease that is at least partially mediated by antibodies to DNA. In this disease, the inflammation caused by deposition of complex formations of anti-DNA antibodies with circulating DNA within tissues is reduced by reason of the extracorporeal treatment of the blood.
In the case of the immunological reactant being an antigen-antibody complex, the treatment consists of two steps. The first step is to pass the plasma through a first chamber having an immunoadsorbent agent which is a specific enzyme whose function is to break down the complex followed by passing the treated plasma through a second chamber having a specific immunoadsorbent agent which forms a complex with part or all of the broken down antigen or antibody.
It is believed that the extracorporeal treatment of disease described above is a major improvement over the presently utilized immunosuppression techniques for treating disease. Present immunosuppression techniques utilize an agent which causes suppression of the overall immune response and which have a wide range of undesirable side effects such as leaving the patient susceptible to various forms of infection from the immunosuppression. Such side effects are not incurred with the extracorporeal treatment of the disease.
Since the immunological reactants are found in the plasma portion of blood, the efficiency of the immunoadsorbent agent can be increased by having only the plasma portion of the blood circulating through the treatment chamber. Also, if whole blood is circulated through the treatment chamber, the efficiency of the immunoadsorbent agent is decreased because particulate matter, such as platelets, etc., can become lodged against and adhere to the coated vehicle thus covering many of the binding sites of the immunoadsorbent agent and preventing their functioning as a filter.
Accordingly the plasma is first separated from the whole blood with a centrifuge device such as that found in the "Celltrifuge".TM. machine sold by American Instrument Company, a Division of Travenol Laboratories, Inc. Silver Spring, Md. or such as that found in the "Cell Separator".TM. machine sold by Fenwal Division of Travenol Laboratories, Inc. Round Lake, Ill. The "Cell Separator" machine is preferred since it also separates (filters out) platelets from the plasma to provide platelet-poor plasma. This is important since platelets tend to attach themselves to the immunoadsorbent agent and "gum up" the plasma treatment chamber.
Various vehicles have been proposed and the controlling factor in selecting a vehicle is the surface area provided by the vehicle.
Collodion charcoal, nylon microspheres and a collodion membrane have been proposed for use as the vehicle.
To provide a substantial surface area on a membrane, it has also been proposed to provide a spiral coiled membrane and gauze backing. The coil is placed in a cylindrical chamber and plasma percolates axially through the coil. The gauze backing however, limits the flow through the coil and the fibers thereof cover a significant area of the membrane.
Various techniques have been proposed for attaching the immunoadsorbent agent to the vehicle. In one technique, a collodion is sprayed on the vehicle, the particular collodion serving to immobilize and bind the immunoadsorbent agent to the surface of the vehicle.
Another technique for producing the same desired result is to spray cyanogen bromide onto the vehicle, chemically changing the surface of the vehicle, thereby permitting the immunoadsorbent agent to bind to the vehicle surface.
The attachment of the immunoadsorbent agent to the vehicle should be such as to allow no, or only minimal, escape of the immunoadsorbent agent and thus eliminate any possibility of toxicity to the patient's biochemical and hematological status.
As will be described in greater detail hereinafter, the apparatus of the present invention provides improved plasma treatment chambers one of which utilizes a coiled membrane with the convolutions thereof spaced apart to permit plasma to flow freely axially of the membrane through the space between convolutions and another of which is designed in such a manner as to provide different flow rates of plasma through the chamber thereby to cause some turbulence in the plasma flow to enhance contact of immunological reactants with the immunoadsorbent agent on a particulate vehicle.